Dendrons are used as versatile building blocks in organic chemistry in order to design stereochemically defined macromolecules or polymers with desired solubility, polarity, amphiphilic, molecular aggregation, biological activity, reactivity, catalytical, and photochemical properties. Among the various types of dendritic building blocks, the 1→3 C-branched polyamide dendrimers are of interest due to their high branching multiplicity and bulkiness as well as the hydrophilicity of their corresponding unprotected polyacids.
The dendritic polymers which may be used in the practice of this invention include generally any of the known dendritic architectures including dendrimers, regular dendrons, controlled hyperbranched polymers, dendrigrafts, and random hyperbranched polymers. Dendritic polymers Lire polymers with densely branched structures having a large number of reactive groups. A dendritic polymer includes several layers or generations of repeating units which all contain one or more branch points. Dendritic polymers, including dendrimers and hyperbranched polymers, are prepared by condensation reactions of monomeric units having at least two different types of reactive groups.
Dendrimers are comprised of a plurality of dendrons that emanate from a common core which can be a single atom or a group of atoms. Each dendron generally consists of terminal surface groups, interior branch junctures having branching functionalities greater than or equal to two, and divalent connectors that covalently connect neighboring branching junctures. Dendrons and dendrimers can be prepared by convergent or divergent synthesis. Divergent synthesis of dendrons and dendrimers involves a molecular growth process which occurs through a consecutive series of geometrically progressive step-wise additions of branches upon branches in a radially outward molecular direction to produce an ordered arrangement of layered branch cells, in which each macromolecular includes a core cell, one or more layers of internal cells, and an outer layer of surface cells, wherein each of the cells includes a single branch juncture. The cells can be the same or different in chemical structure and branching functionality. The surface branch cells may contain either chemically reactive or passive functional groups. Chemically reactive surface groups can be used for further extension of dendritic growth or for modification of dendritic molecular surfaces. The chemically passive groups may be used to physically modify dendritic surfaces, such as to adjust the ratio of hydrophobic to hydrophilic terminals. Convergent synthesis of dendrimers and dendrons involves a growth process which begins from what will become the surface of the dendron or dendrimer and progresses radially in a molecular direction toward a focal point or cove.
A third method by which dendrimers and dendrons can be prepared is by using a one-pot synthesis in which dendritic polymers are prepared by a step-growth polymerization reaction of a single type of monomer having a single reactive group of a first type (B) and a plurality (y) of reactive groups of a second type (A), i.e., a B-Ay type monomer, which is initiated by a core having a plurality (x) of the A type reactive groups, wherein A groups can react with B groups, but not with other A groups, and B groups cannot react with other B groups. The one-pot synthesis method is simpler and less expensive than the divergent and convergent synthesis methods. However, the one-pot synthesis method lacks reaction control, which leads to more polydispersed products with larger deviations from ideal dendron structure.
Hyperbranched polymers represent a class of dendritic polymers which contain high levels of non-ideal irregular branching arrays as compared with the more nearly perfect regular structure of dendrons and dendrimers. Specifically, hyperbranched polymers contain a relatively high number of irregular branching arrays in which not every repeat unit contains a branch juncture. Consequently, hyperbranched polymers may be viewed as intermediate between randomly branched polymers and regular dendrons and dendrimers, yet dendritic, because of their relatively high branch-juncture content per individual macromolecule.
Both in the convergent construction of dendrimers and in the dendrimerization or dendron-coating of materials and surfaces, dendrons of different size and surface coatings have been shown to play key role. For example, the 1→3 C-branched monomer, di-tert-butyl 4-[2-tert-butoxycarbonyl)ethyl]-4-aminoheptanedioate, “Behera's Amine”, was developed and its use in the divergent synthesis of a family of amide-connected dendrimers was demonstrated. The facile conversion of Behera's amine to a corresponding isocyanate has further expanded its utilitarian uses. There was further convergently created the related second and third generation dendrons. These 1→3 C-branched monomers are easily attached to a particular core, have a specific molecular structure and are easily transformed to the corresponding acidic surface.
The convergent route used to generate the higher generation dendrons used the typical amidation coupling reaction in which a combination of dicyclohexylcarbodiimide (DCC) and 1-hydroxy-benzotriazole (1-HOBT) in dimethylformamide (DMF) were used as reagents of choice. In general, the yields were generally moderate and the desired products were difficult to purify given the formation of dicyclohexyl urea (DCU), which is highly insoluble in most common organic solvents.
It would be advantageous to provide a route of synthesis requiring fewer steps than the aforementioned methods. More particularly, it would be advantageous to provide a route of synthesis that generates a high-yield of pure 1→3 C-branched dendrimers without the use of DCC and 1-HOBT and devoid of DCU unless it is present as a contaminant in a separate reactant used in the route of synthesis.